Summary

The inclusion of the Arctic mutation along with the Swedish mutation in the transgene results in more prominent Aβ pathology, including elevated soluble Aβ aggregates such as Aβ protofibrils, greater accumulation of Aβ inside neurons, and more robust senile plaques than typically observed with the Swedish mutation alone (e.g. Tg-Swe).

Similar to postmortem Alzheimer's disease brain, biochemical dissolution of deposited Aβ in this model requires formic acid (Philipson et al., 2009). In the double mutant mice, intraneuronal Aβ aggregation is first observed at one monthof age (Lord et al., 2006; Philipson et al., 2009) and extracellular plaque deposition starts at around five to six months of age (Lord et al., 2006). Congophilic parenchymal plaque deposition is usually the dominating neuropathological feature, but some individual mice show high levels of CAA, which is usually most pronounced in the thalamus. Aβ protofibrils can be detected in brain TBS extracts from mice at two months of age and peak around 12-14 months of age(Lord et al., 2009). The plaques in these mice have a different morphological structure as compared to transgenic mice bearing the Swedish mutation alone, in that they have been shown to emit fluorescence at different wavelengths when stained with luminescent polymers (conformational amyloid ligands). The plaque population is also more homogenous in size and structure as compared to Tg-Swe, with plaque consistently most evident in the cerebral cortex, hippocampus and thalamus(Lillehaug et al., 2013). An anatomic atlas of the Tg-ArcSwe model is available at the Rodent Brain Workbench. At four months, cerebrospinal fluid levels of Aβ are elevated, and CSF tau protofibrils can also be detected (personal communication, Lars Nilsson).

Modification Details

Phenotype Characterization

When visualized, these models will distributed over a 18 month
timeline
demarcated at the following intervals: 1mo, 3mo, 6mo,
9mo, 12mo, 15mo, 18mo+.

Absent

Neuronal Loss

Tangles

No Data

Synaptic Loss

Changes in LTP/LTD

Plaques

Extracellular amyloid plaque deposition starts at around 5-6 months of age (Lord et al., 2006) and is most consistently present in the cerebral cortex, hippocampus, and thalamus (Lillehaug et al., 2013).

Tangles

Absent.

Neuronal Loss

Absent.

Gliosis

Microgliosis and astrogliosis most prominent in the hippocampus, but also locally around deposits in the cerebral cortex and thalamus.